The planned investigation will deal with the mechanism (pathogenesis) and function of fever. Specifically, we will attempt to characterize the physical nature, molecular weight, and isoelectric point of a human lymphokine which activates macrophages to release endogenous pyrogen. In addition, we will examine the nature of the macrophage cell receptor for this lymphokine and determine the type(s) of lymphocyte(s) which secrete(s) this substance. We will also study the ability of immune complexes to stimulate EP production in vitro. In other work we will examine the role of prostaglandin E in brain tissues (e.g., hypothalamus) from rabbits made febrile by intravenous injection of endogenous pyrogen. Similar studies will be done in vitro by incubating rabbit brain slices with purified endogenous pyrogen and determining the amount of prostaglandin E that these slices release. In order to study the function of fever we will continue past experiments with the desert iguana, a poikilothermic (or cold-blooded) vertebrate which has many immunologic similarities to mammals. Since fever has been shown to be beneficial in iguanas infected with bacteria we will study the effect of elevated temperature on the production of chemotactic factors (e.g., C5a), the exudation of leukocytes, and bacterial clearance.